Arachidonic acid sex-dependently affects obesity through linking gut microbiota-driven inflammation to hypothalamus-adipose-liver axis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Zhuang, Pan²  Shou, Qiyang^3,4  Lu, Yanhua⁵  Wang, Guangfa⁶  Qiu, Jieni¹  Wang, Jun²  He, Lilin²  Chen, Jingnan²  Jiao, Jingjing¹  Zhang, Yu² 

[1] Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Nutr, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Biosyst Engn & Food Sci, Natl Engn Lab Intelligent Food Technol & Equipmen, Zhejiang Key Lab Agrofood Proc,Full Inst Food Sci, Hangzhou 310058, Zhejiang, Peoples R China

[3] Zhejiang Chinese Med Univ, Expt Anim Res Ctr, Hangzhou 310053, Zhejiang, Peoples R China

[4] Zhejiang Chinese Med Univ, Inst Comparat Med, Hangzhou 310053, Zhejiang, Peoples R China

[5] Hangzhou Normal Univ, Sch Med, Inst Aging Res, Hangzhou 311121, Zhejiang, Peoples R China

[6] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept PET Ctr, Hangzhou 310003, Zhejiang, Peoples R China

关键词: Arachidonic acid;    Obesity;    Sexual dimorphism;    Gut microbiota;    Butyrate;    Hypothalamus-adipose-liver axis;   

DOI  :  10.1016/j.bbadis.2017.07.003

来源: Elsevier

【 摘 要 】

Unraveling the role of dietary lipids is beneficial to treat obesity and metabolic dysfunction. Nonetheless, how dietary lipids affect existing obesity remains unknown. Arachidonic acid (AA), a derivative of linoleic acid, is one of the crucial n-6 fatty acids. The aim of this study was to investigate whether AA affects obesity through associating microbiota-driven inflammation with hypothalamus-adipose-liver axis. Four-week old C57BL/6 J mice were fed with a high-fat diet (HFD, 45% fat) for 10 weeks to induce obesity, and then fed a HFD enriched with 10 g/kg of AA or a continuous HFD in the following 15 weeks. Systemic adiposity and inflammation, metabolic profiles, gut microbiota composition, short-chain fatty acids production, hypothalamic feeding regulators, browning process of adipocytes, hepatosteatosis, and insulin resistance in adipose were investigated. The results indicated that AA aggravates obesity for both genders whereas sex-dependently affects gut microbiota composition. Also, AA favors pro-inflammatory microbiota and reduces butyrate production and circulating serotonin, which augments global inflammation and triggers hypothalamic leptin resistance via microglia accumulation in male. AA exacerbates non-alcoholic steatohepatitis along with amplified inflammation through TLR4-NF-kappa B pathway and induces insulin resistance. Reversely, AA alleviates obesity-related disorders via rescuing anti-inflammatory and butyrate-producing microbiota, up-regulating GPR41 and GPR109A and controlling hypothalamic inflammation in female. Nevertheless, AA modifies adipocyte browning and promotes lipid mobilization for both genders. We show that AA affects obesity likely through a gut-hypothalamus-adipose-liver axis. Our findings formulate recommendations of n-6 fatty acids like AA from dietary intake for obese subjects preferably in a sexually dimorphic way.

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